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CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression
Authors:Yuluo Wu  Haiyang Zhao
Institution:1.Department of Oncology, Guangdong Medical University Affiliated Central People''s Hospital of Zhanjiang, Zhanjiang, Guangdong 524000, P.R. China;2.Department of Oncology, Beijing Zhongguancun Hospital, Beijing 100190, P.R. China
Abstract:Drug resistance is a key factor affecting the treatment of gastric cancer. The resistance of gastric cancer cells to anticancer drugs, such as cisplatin (DDP), remains a major challenge to patient recovery. The present study aimed to investigate the roles of C-terminal-binding protein 1 (CTBP1) in the DDP resistance of gastric cancer cells and to determine its regulatory effect on DNA repair protein RAD51 homolog 1 (RAD51). The DDP-resistant human gastric cancer AGS and HGC cell lines, AGS/DDP and HGC-27/DDP, respectively, were established and CTBP1 expression was detected by western blotting. In addition, Cell Counting Kit-8, colony formation and flow cytometry assays were performed to detect the proliferation and apoptosis of these two cell lines following CTBP1 knockdown. The expression levels of apoptosis-related proteins were detected by western blotting. In addition, RAD51 was overexpressed in CTBP1 knockdown cells, and proliferation and apoptosis were subsequently determined using the aforementioned methods. The results demonstrated that CTBP1 expression was notably increased in DDP-resistant gastric cancer cells. Furthermore, CTBP1 knockdown suppressed the proliferation and induced the apoptosis of AGS/DDP and HGC-27/DDP cells. Notably, CTBP1 promoted RAD51 expression in DDP-resistant gastric cancer cells. Overexpression of RAD51 in CTBP1 knockdown AGS/DDP and HGC-27/DDP cells rescued the proliferation and alleviated the apoptosis of these cells. Taken together, the results of the present study suggested that CTBP1 may enhance the DDP resistance of gastric cancer cells by activating RAD51 expression, thus providing a potential novel therapy (CTBP1 knockdown) for the clinical treatment of patients with gastric cancer.
Keywords:gastric cancer  cisplatin resistance  C-terminal-binding protein 1  DNA repair protein RAD51 homolog 1  proliferation
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